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Background. Information on prescribing quality is increasingly used by policy makers, insurance companies and health care providers. For reliable assessment of prescribing quality it is important to correctly identify the patients eligible for recommended treatment. Often either diagnostic codes or clinical measurements are used to identify such patients. We compared these two approaches regarding the outcome of the prescribing quality assessment and their ability to identify treated and undertreated patients. Methods. The approaches were compared using electronic health records for 3214 diabetes patients from 70 general practitioners. We selected three existing prescribing quality indicators (PQI) assessing different aspects of treatment in patients with hypertension or who were overweight. We compared population level prescribing quality scores and proportions of identified patients using definitions of hypertension or being overweight based on diagnostic codes, clinical measurements or both. Results. The prescribing quality score for prescribing any antihypertensive treatment was 93% (95% confidence interval 90-95%) using the diagnostic code-based approach, and 81% (78-83%) using the measurement-based approach. Patients receiving antihypertensive treatment had a better registration of their diagnosis compared to hypertensive patients in whom such treatment was not initiated. Scores on the other two PQI were similar for the different approaches, ranging from 64 to 66%. For all PQI, the clinical measurement -based approach identified higher proportions of both well treated and undertreated patients compared to the diagnostic code -based approach. Conclusions. The use of clinical measurements is recommended when PQI are used to identify undertreated patients. Using diagnostic codes or clinical measurement values has little impact on the outcomes of proportion-based PQI when both numerator and denominator are equally affected. In situations when a diagnosis is better registered for treated than untreated patients, as we observed for hypertension, the diagnostic code-based approach results in overestimation of provided treatment. © 2010 Martirosyan et al.

Background: In Europe, Direct Healthcare Professional Communications (DHPCs) are important tools to inform healthcare professionals of serious, new drug safety issues. However, this tool has not always been successful in effectively communicating the desired actions to healthcare professionals.Objective: The aim of this study was to explore healthcare providers' experiences and their preferences for improvement of risk communication, comparing views of general practitioners (GPs), internists, community pharmacists and hospital pharmacists.Methods: A questionnaire was developed and pilot tested to assess experiences and preferences of Dutch healthcare professionals with DHPCs. The questionnaire and two reminders were sent to a random sample of 3488 GPs, internists and community and hospital pharmacists in the Netherlands. Descriptive statistics were used to describe demographic characteristics of the respondents. Chi squares, ANOVAs and the Wilcoxon signed rank test were used, when appropriate, to compare healthcare professional groups.Results: The overall response rate was 34% (N = 1141, ranging from 24% for internists to 46% for community pharmacists). Healthcare providers trusted safety information more when provided by the Dutch Medicines Evaluation Board (MEB) than by the pharmaceutical industry. This was more the case for GPs than for the other healthcare professionals. Respondents preferred safety information to be issued by the MEB, the Dutch Pharmacovigilance Center or their own professional associations. The preferred alternative channels of drug safety information were e-mail, medical journals and electronic prescribing systems.Conclusions: Safety information of drugs does not always reach healthcare professionals through DHPCs. To improve current risk communication of drug safety issues, alternative and/or additional methods of risk communication should be developed using electronic methods and medical journals. Moreover, (additional) risk communication coming from an independent source such as the MEB should be considered. Special effort is needed to reach GPs. [ABSTRACT FROM AUTHOR]

Background: Non-serious symptomatic adverse drug events (ADEs) affect the real benefit-risk ratio of a drug. Currently, such ADEs are quantified in different ways, often using reports from a healthcare provider or patients, resulting in large variations in estimated rates. Several studies showed that patients report bothersome or symptomatic ADEs more frequently than providers, but no comparisons to an external reference or gold standard have been made.Objective: We conducted a literature review to assess the agreement and concurrent validity of healthcare provider- and patient-oriented methods for quantifying symptomatic ADEs of oral blood glucose-lowering drugs in patients with type 2 diabetes mellitus.Methods: We systematically searched MEDLINE and EMBASE databases for observational studies reporting on rates of ADEs in patients treated for type 2 diabetes that were published between 1999 and 2011. We included nine observational studies reporting absolute rates of symptomatic ADEs in patients receiving monotherapy. We calculated 95% confidence intervals and assessed agreement between rates observed with different methods. We assessed concurrent validity using the range noted in the Summary of Product Characteristics (SPC) as the gold standard.Results: A comparison of rates reported by patients and providers was only possible using three studies of metformin that assessed mainly gastrointestinal (GI) ADEs. Provider-oriented methods by means of medical record review gave lower rates for abdominal pain (0.6-3.7%), dyspepsia (1.3-2.8%) and constipation (0.6-1.0%) than a patient questionnaire method (8.5%, 11.9% and 20.7%, respectively). For diarrhoea, the patient-reported rate (5.2%) was in agreement with the provider-based rates (1.6-7.6%). The majority of the rates reported by providers and patients were not corresponding with the ranges in the SPC. For GI ADEs the rates were all lower, whereas for lactic acidosis and hypoglycaemia the rates were higher.Conclusion: Although it has repeatedly been proposed that patients' reports on safety should be incorporated with providers' reports, especially for symptomatic ADEs, the number of observational studies using patient-oriented methods for assessing ADEs other than hypoglycaemia are limited. Provider-based measurement tended to underestimate symptomatic ADEs. Patient-oriented methods seemed to give ADE rates that were closer to the rates reported in the SPC. [ABSTRACT FROM AUTHOR]

Background: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required ≥1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval.Objective: The aim was to evaluate the extent to which regulators and industry have addressed the risk of safety issues for HIV drugs based on prior experience with other drugs in the same class and whether doing so impacts development time of these drugs.Methods: HIV drugs receiving ≥1 DHPC in the Netherlands between January 1999 and December 2008 were identified. Each drug with a DHPC ('index' drug) was paired with subsequently approved HIV drug(s) in the same class (Anatomical Therapeutic Chemical [ATC] 4th level) ['follow-on' drugs]. Characteristics of safety issues were extracted from the DHPCs of the 'index' drugs. European Public Assessment Reports (EPARs) were reviewed regarding whether the safety issues had been considered during development and approval. Consideration of previously identified safety issues in 'follow-on' drug applications was assessed regarding attention paid to adverse drug reaction (ADR) symptoms in pre-marketing studies, Summary of Product Characteristics (SmPC) and postmarketing commitments, and whether size of the safety population was in accordance with Regulatory guidelines. 'Index' drugs were also paired with drugs in the same class already on the market ('older' drugs). For 'older' drugs, we identified whether the safety issue led to appropriate changes in the current SmPC (January 2011) compared with the SmPC at the time of marketing authorization. Clinical development time was assessed using time from first patent application to market authorization as proxy, and comparison was made between 'index' and 'follow-on' drugs.Results: For 9 (43%) of the 21 centrally authorized HIV drugs, 11 serious safety issues that required a DHPC were identified. Two drugs were excluded from our analysis (DHPCs related to contamination/medication error). Six 'index' drugs were paired, each with one to six 'follow-on' drugs. Three concerned drug-drug interactions (DDIs); the other three were intracranial haemorrhage, neuromuscular weakness and severe skin/hepatic reactions. All but one 'follow-on' drug had information in the EPAR on that specific ADR (i.e. attention was paid to the ADR). The DDIs were addressed in pre-marketing studies and/or the SmPC. Two of the other ADRs were addressed by postmarketing surveillance commitments; intracranial haemorrhage was not addressed. Three safety issues for two 'index' drugs could not be paired with a 'follow-on' drug as no drug in the same class was approved after the corresponding DHPCs were issued. Five of the nine safety issues were added to at least one of the current SmPCs for the 'older' drugs already on the market at the time of DHPC issue. Two safety issues were already in the SmPC of the 'older' drugs at time of market approval and two were not introduced into the SmPC of 'older' drugs. Population size to assess short-term safety complied with the guidelines for four 'index', seven 'follow-on' and three 'older' drugs; population size to assess long-term safety complied for one, three and two drugs, respectively. For five drugs, EPARs did not provide adequate information on population size. No statistically significant difference in development time between 'index' and 'follow-on' drugs was found.Conclusion: Generally, safety issues were taken into account in the approval process of other drugs in the class. The approaches were different and determined by the nature of the ADR. Taking safety issues into account in the approval process did not seem to impact on the time taken to perform the pre-approval clinical programme. [ABSTRACT FROM AUTHOR]

Background: Medication safety research and clinical pharmacy practice today is primarily focused on managing preventable adverse drug events (pADEs). Determinants of both pADEs and non-preventable adverse drug reactions (ADRs) have been identified. However, relatively little is known on the overlap between these determinants and the balance of preventable and non-preventable harm inpatients experience in modern computerized hospitals.Objective: The aim of this study was to analyse the prevalence of pADEs and non-preventable ADRs as well as the determinants, including multimorbidity, of these ADEs, i.e. both pADEs and ADRs.Methods: Adverse events experienced by patients admitted to two Dutch hospitals with functioning computerized physician order entry (CPOE) systems were prospectively identified through chart review. Adverse events were divided into pADEs (i.e. as a result of a medication error) and non-preventable ADRs. In both cases, a causal relationship between adverse events and patients' drugs was established using the simplified Yale algorithm. Study data were collected anytime between April 2006 and May 2008 over a 5-month period at each hospital ward included in the study, beginning from 8 weeks after CPOE was implemented at the ward.Results: pADEs and non-preventable ADRs were experienced by 349 (58%) patients, of whom 307 (88%) had non-preventable ADRs. Multimorbidity (adjusted odds ratio [OR(adj)] 1.90; 95% CI 1.44, 2.50; OR(adj) 1.28; 95% CI 1.14, 1.45, respectively), length of stay (OR(adj) 1.13; 95% CI 1.06, 1.21; OR(adj) 1.11; 95% CI 1.07, 1.16, respectively), admission to the geriatric ward (OR(adj) 7.78; 95% CI 2.15, 28.13; OR(adj) 3.82; 95% CI 1.73, 8.45, respectively) and number of medication orders (OR(adj) 1.25; 95% CI 1.16, 1.35; OR(adj) 1.13; 95% CI 1.06, 1.21, respectively) were statistically significantly associated with pADEs and ADRs. Admission to the gastroenterology/rheumatology ward (OR(adj) 0.22; 95% CI 0.06, 0.77; OR(adj) 0.40; 95% CI 0.24, 0.65, respectively) was inversely related to both pADEs and ADRs. Other determinants for ADRs only were female sex (OR(adj) 1.77; 95% CI 1.12, 2.80) and use of drugs affecting the nervous system (OR(adj) 1.83; 95% CI 1.09, 3.07). Age was a significant determinant for pADEs only (OR(adj) 1.07; 95% CI 1.03, 1.11).Conclusions: In this study more than half of the patients admitted to the hospitals are harmed by drugs, of which most are non-serious, non-preventable ADRs (after the introduction of CPOE). Determinants of both pADEs and ADRs overlap to a large extent. Our results imply the need for signalling early potential adverse events that occur during the normal use of drugs in multimorbid patients or those in geriatric wards. Subsequent therapeutic interventions may improve the well-being of hospitalized patients to a greater extent than focusing on errors in the medication process only. [ABSTRACT FROM AUTHOR]

Background: As pre-approval trials are inherently limited in assessing the complete benefit-risk profile of a new drug, serious safety issues may emerge once a drug gains widespread use after approval. Regulators face the dilemma of balancing timely market access with the need for complete data on risks. This challenge has led to a life-cycle approach but, so far, few data are available on post-approval safety issues requiring regulatory action.Objective: The aim of this study is to determine the frequency, timing and nature of safety issues that necessitated safety-related regulatory action in the form of a Direct Healthcare Professional Communication (DHPC) issued by pharmaceutical companies in collaboration with the Dutch Medicines Evaluation Board during the past decade.Methods: All DHPCs issued in the Netherlands from 1 January 1999 to 1 January 2009 were retrospectively collected from the national regulatory authorities. Elapsed time between the approval date and the issue of the DHPC was determined. Characteristics of the action including the nature of the safety issue (according to Medical Dictionary for Regulatory Activities [MedDRA] terminology), type of drug and procedural aspects of the regulatory action taken were reviewed. DHPC characteristics were tabulated and explorative non-parametric tests were performed to study the effect of safety issue, drug class, drug type, orphan drug and first-in-class status on elapsed time from approval to the DHPC.Results: 157 DHPCs were issued concerning 112 different active substances, approximately 9% (112/1200) of active substances available in the Netherlands in 2007. The number of DHPCs issued increased by 2.1 (95% CI 1.2, 3.1; p < 0.001) DHPCs per year over the past decade, reaching a total of 25 in 2008. The median time between approval and DHPC was 5.3 years (range 0.13-48 years). No significant trend in elapsed time to DHPC was observed in relation to the studied years (p = 0.06). One-third of all DHPCs were issued in the first 3 years after approval, but 27% (n = 43/157) of the DHPCs were issued 10 or more years after approval. Timing of DHPCs differed depending on safety issue, drug class, drug type and orphan drug status. DHPCs mostly concerned adverse events in the system organ class of 'cardiac disorders' (15%), 'injury, poisoning and procedural complications' (13%) and 'general disorders and administration site conditions' (10%). In ten cases the drug was eventually withdrawn. Withdrawal occurred a median duration of 2.4 years after registration (range of 1.5-48 years) and was most frequently due to cardiac disorders (including QT interval prolongation; four occasions) and hepatobiliary disorders (two occasions).Conclusions: In the past decade, the number of DHPCs has increased over time. This is likely caused by a multitude of factors: increased risk awareness by the public, media, regulators and other stakeholders; the type of drugs approved, such as orphan drugs and biologicals; and the regulatory process, including conditional approvals. The number of DHPCs may in the future increase further with the possibility of screening large epidemiological databases proactively for adverse drug events. Nine percent of all marketed drugs required a safety-related action. Regulatory action is taken shortly (<3 years) after market approval nearly as often as after intermediate (3-10 years) and long-term (>10 years) market exposure. These findings underline the need for risk management during the whole life cycle of a drug. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a major public health problem among the elderly. The syndrome of HF may arise in the presence of either a depressed or apparently normal left-ventricular ejection fraction (LVEF). The latter entity is more common in the elderly. In elderly patients with HF, prescription of a beta-adrenoceptor antagonist may raise concerns regarding efficacy and tolerability. Because of these concerns, but also as a result of a paucity of published data, beta-adrenoceptor antagonists are under-prescribed to elderly patients with HF in general practice.We review the evidence regarding the efficacy and tolerability of beta-adrenoceptor antagonist therapy in elderly patients with HF. We found three major sources of evidence: one prospective, randomised controlled trial (RCT), SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure); a subgroup meta-analysis of elderly patients included in systolic HF trials; and a large number of observational studies. SENIORS showed that the third-generation beta-adrenoceptor antagonist nebivolol reduces the risk of all-cause mortality or cardiovascular admission in elderly patients (aged >/=70 years) with HF and a broad range of LVEF. The subgroup meta-analysis of RCTs showed that beta-adrenoceptor antagonists reduce mortality in elderly patients (aged 60-80 years) with systolic HF, and that the benefit is similar to that observed in non-elderly patients (aged <60 years). The observational studies showed a beneficial effect of beta-adrenoceptor antagonists in elderly populations in daily practice, including those with depressed and preserved LVEF. However, the effect of beta-adrenoceptor antagonists on all-cause mortality may be lower in very elderly patients (aged >75 years). Approximately two-thirds of elderly patients with HF tolerate a beta-adrenoceptor antagonist, but only 40-70% of the target doses recommended in RCTs are achieved. Some clinical variables may predict low beta-adrenoceptor antagonist tolerability, such as low systolic blood pressure, higher New York Heart Association HF severity class, advanced age and ischaemic cause of HF. Furthermore, prescription of a high diuretic dose and calcium channel antagonists may also decrease beta-adrenoceptor antagonist tolerability. However, it is difficult to identify on clinical grounds patients intolerant to any beta-adrenoceptor antagonist dose. Low-dose therapy (<50% target dose) may be effective in an elderly population with HF, but prescription of at least a medium dose (>/=50% target dose) may achieve a higher benefit.In conclusion, although elderly patients with HF take lower doses of beta-adrenoceptor antagonists, these agents are still effective and overall well tolerated in this population. Elderly patients with HF should therefore not be denied beta-adrenoceptor antagonist therapy. The dilemma relies on dose-benefit balance, as higher doses would be more effective but may raise tolerability concerns. The beneficial effects of use of beta-adrenoceptor antagonists in elderly patients with HF and preserved LVEF need to be further confirmed in large RCTs. [ABSTRACT FROM AUTHOR]

Many studies have been done to document drug use patterns, and indicate that overprescribing, multi-drug prescribing, misuse of drugs, use of unnecessary expensive drugs and overuse of antibiotics and injections are the most common problems of irrational drug use by prescribers as well as consumers. Improving drug use would have important financial and public health benefits. Many efforts have been undertaken to improve drug use, but few evaluations have been done in this field. This article provides an overview of 50 intervention studies to improve drug use in developing countries. It highlights what type of interventions exist and what is known about their impact. [ABSTRACT FROM PUBLISHER]

Background: Antibiotics are widely-used medicines for which a more prudent use has been advocated to minimize development of resistance. There are considerable cross-national differences that can only partially be explained by epidemiological difference and variations in health care structure. The aim of this study was to explore whether cross-national differences in use of antibiotics (prescribed and non-prescribed) are associated with differences between national cultures as described in Hofstede's model of cultural dimensions (Power Distance, Individualism, Masculinity, Uncertainty Avoidance and Long-Term Orientation).Methods: Country-level data of prescribed antibiotic use and self-medication with antibiotics were correlated to country-specific scores of cultural dimensions obtained from Hofstede. Data on use of antibiotics were provided by three European studies, based on different methods and/or countries: Self-medication with Antibiotics and Resistance in Europe (SAR), based on a survey in 2003 on reported use of antibiotics in 19 countries, the European Surveillance on Antimicrobial Consumption, based on distribution and reimbursement of antibiotics in ambulatory care (1997-2002), and the 2002 interview-based Eurobarometer study, asking whether respondents had taken antibiotics in the previous 12 months. These studies provided data on antibiotics use for 27 European countries in total, for which scores of cultural dimensions were also available. The SAR-study differentiated between prescribed antibiotics and self-medication with antibiotics.Results: Significant positive correlations were found for Power Distance Index with use of prescribed antibiotics in the three studies (rho between 0.59 and 0.62) and with self-medication (rho = 0.54) in the SAR study. Positive significant correlations were found for the Uncertainty Avoidance Index with the use of antibiotics as reported in two studies (rho between 0.57 and 0.59; for the SAR study the correlations were insignificant). Masculinity was not significantly correlated, except in one study after controlling for GDP (r = 0.81). For Individualism and Long-Term Orientation no significant correlations were found.Conclusion: Power Distance is a cultural aspect associated with antibiotic use, suggesting that the culture-specific way people deal with authority is an important factor in explaining cross-national differences in antibiotic use. There are indications that Uncertainty Avoidance also plays a role but further research is needed to better understand the complex effect of cultural dimensions. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study is to determine to what extent barriers perceived by general practitioners (GPs) for prescribing angiotensin-converting enzyme inhibitors (ACE-I) in chronic heart failure (CHF) patients are related to underuse and underdosing of these drugs in actual practice. METHODS: Barriers were assessed with a semi-structured questionnaire. Prescribing data were extracted from GPs' computerised medical records for a random sample of their CHF patients. Relations between barriers and prescribing behaviour were assessed by means of Spearman rank correlation and multivariate regression modelling. RESULTS: GPs prescribed ACE-I to 45% of their patients and had previously initiated such treatment in an additional 3.5%, in an average standardised dose of 13.5 mg. They perceived a median of four barriers in prescribing ACE-I or optimising ACE-I dose. Many GPs found it difficult to change treatment initiated by a cardiologist. Furthermore, initiating ACE-I in patients already using a diuretic or stable on their current medication was perceived as barrier. Titrating the ACE-I dose was seen as difficult by more than half of the GPs. No significant relationships could be found between the barriers perceived and actual ACE-I prescribing. Regarding ACE-I dosing, the few GPs who did not agree that the ACE-I should be as high as possible prescribed higher ACE-I doses. CONCLUSION: Variation between GPs in prescribing ACE-I for CHF cannot be explained by differences in the barriers they perceive. Tailor-made interventions targeting only those doctors that perceive a specific barrier will therefore not be an efficient approach to improve quality of care. [ABSTRACT FROM AUTHOR]

Cultural differences are probably an important factor in the considerable variation in antibiotic use between countries. The objective of this study was to explore local cultural differences in the lay perspective on coping with URTD and using antibiotics. We interviewed 30 persons in a Dutch and a Belgian city. Twenty-one were interviewed a second time after 3 months. Between the first and second interview, they noted in a diary all URTD episodes experienced by themselves and their family members (N=69) and how they coped with them. The Dutch participants labelled most URTD episodes as "common cold" or "flu". The Flemish participants labelled most of their URTD episodes as "bronchitis" and used more antibiotics. Four categories of antibiotic users could be distinguished. Participants with a Protestant background were more sceptical about medicines than those with a Catholic background. A thorough understanding of the cultural context is necessary to design effective campaigns to promote rational antibiotic use. [ABSTRACT FROM AUTHOR]

Aims: Understanding how much healthcare professionals (HCPs) know about medication can help in devising strategies to improve rational medication use. This study aimed to synthesize information on the level of medication knowledge of HCPs in Africa., Method: We performed a systematic literature study in Embase and PubMed. We included original studies quantifying HCPs' medication knowledge, published between 2012 and 2016. We extracted disease focus, country, number and type of HCPs included and all medication-related knowledge questions and scored the quality of papers. The outcome measure was the percentage of HCPs who correctly answered medication knowledge questions., Results: We identified 64 studies from 12 African countries, comprising 13 911 HCPs, mostly nurses/midwifes and physicians. We extracted 306 medication-related knowledge questions, and only 52% (SD 28) of HCPs correctly answered them. Knowledge questions were mainly about medication prescribed for communicable diseases (70%), followed by non-communicable diseases (11%), and family planning/gynaecology (10%). Most papers concluded that there was a considerable medication knowledge gap among HCPs., Conclusion: We found a low level of medication knowledge across different disease areas, countries and HCPs. This underlines the continuous need to strengthen the undergraduate and postgraduate education in (clinical) pharmacology and therapeutics in Africa., (© 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Decision aids can be used to support shared decision making (SDM). A patient-oriented treatment decision aid (DA) was developed for type 2 diabetes but its use by general practice staff appeared to be limited., Objectives: To explore views of practice staff towards SDM and the DA., Design: A mixed-methods study within the Dutch PORTDA-diab trial., Setting and Participants: Included were 17 practices with staff members who were responsible for routine diabetes care and had worked with the DA, and 209 of their patients., Methods: Interviews were conducted focusing on applicability, usefulness and feasibility of the DA. Interviews were tape-recorded, transcribed verbatim and subjected to content analysis for identifying and classifying views. Patient-reported data about the use of the DA were collected. Associations between specific views and use of the DA were tested using Pearson point-biserial correlation., Results: The majority of practice staff expressed positive views towards SDM, which was associated with making more use of the DA. Most of the staff expressed that the DA stimulated a two-way conversation. By using the DA, several became aware of their paternalistic approach. Some staff experienced a conflict with the content of the DA, which was associated with making less use of the DA., Conclusions: The DA was considered useful by practice staff to support SDM. A positive view towards SDM was a facilitator, whereas experiencing a conflict with the content of the DA was a barrier for making use of the DA., (© 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.)

Purpose: The STOPP/START criteria are increasingly used to assess prescribing quality in elderly patients at practice level. Our aim was to test computerized algorithms for applying these criteria to a medical record database., Methods: STOPP/START criteria-based computerized algorithms were defined using Anatomical-Therapeutic-Chemical (ATC) codes for medication and International Classification of Primary Care (ICPC) codes for diagnoses. The algorithms were applied to a Dutch primary care database, including patients aged ≥65 years using ≥5 chronic drugs. We tested for associations with patient characteristics that have previously shown a relationship with the original STOPP/START criteria, using multivariate logistic regression models., Results: Included were 1187 patients with a median age of 75 years. In total, 39 of the 62 STOPP and 18 of the 26 START criteria could be converted to a computerized algorithm. The main reasons for inapplicability were lack of information on the severity of a condition and insufficient covering of ICPC-codes. We confirmed a positive association between the occurrence of both the STOPP and the START criteria and the number of chronic drugs (adjusted OR ranging from 1.37, 95% CI 1.04-1.82 to 3.19, 95% CI 2.33-4.36) as well as the patient's age (adjusted OR for STOPP 1.30, 95% CI 1.01-1.67; for START 1.73, 95% CI 1.35-2.21), and also between female gender and the occurrence of STOPP criteria (adjusted OR 1.41, 95% CI 1.09-1.82)., Conclusion: Sixty-five percent of the STOPP/START criteria could be applied with computerized algorithms to a medical record database with ATC-coded medication and ICPC-coded diagnoses., (Copyright © 2017 John Wiley & Sons, Ltd.)

Aims: The aim of the present study was to evaluate the impact of adverse drug events (ADEs) and treatment satisfaction on antihypertensive medication adherence., Methods: A cross-sectional study was conducted in six public hospitals in Ethiopia. We included adult ambulatory patients on antihypertensive medication. Adherence was measured using the eight-point Morisky Medication Adherence Scale, which categorizes as low (0-5), medium (6-7) and high (8) adherence. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4, which included questions about ADEs. Data were analysed using generalized ordered logistic regression with 95% confidence intervals (CIs)., Results: We included 925 out of 968 patients. Overall, 42% of patients scored low, 37% medium and 21% high adherence. Satisfaction with treatment was low, with a mean (standard deviation) TSQM score for global satisfaction of 51 (14). A total of 193 (21%) patients experienced 421 ADEs - mainly dyspeptic symptoms (12%), headache (11%) and cough (11). Experiencing more ADEs reduced the odds of being adherent [low vs. medium/high: odds ratio (OR) OR 1 0.77 (95% CI 0.67, 0.89), and low/medium vs. high: OR 2 0.55 (05% CI 0.41, 0.73)]. Being more satisfied increased the odds of being adherent [low vs. medium/high: OR 1 1.02 (95% CI 1.01, 1.03)]. Taking medication >1 year [OR 1 = 2 , 0.60 (95% CI 0.43, 0.83)] and taking calcium channel blockers [OR 1 = 2 0.71 (95% CI 0.54, 0.92)] decreased the odds for both low vs. medium/high and low/medium vs. high adherence., Conclusions: Only one in five patients reported perfect (high) adherence to their antihypertensive treatment regimen. Experiencing ADEs and being dissatisfied with treatment were associated with lower adherence. In addition to addressing treatment satisfaction and drug safety in first-world countries, these should also be addressed in resource-poor settings, within patient consultations, to enhance adherence., (© 2017 The British Pharmacological Society.)

Objectives: We examined determinants of achieving blood pressure control in patients with hypertension and of treatment intensification in patients with uncontrolled blood pressure (BP)., Design: A retrospective cohort study in six public hospitals, Ethiopia., Participants: Adult ambulatory patients with hypertension and with at least one previously prescribed antihypertensive medication in the study hospital., Outcome: Controlled BP (<140/90 mm Hg) and treatment intensification of patients with uncontrolled BP., Results: The study population comprised 897 patients. Their mean age was 57 (SD 14) years, 63% were females, and 35% had one or more cardiometabolic comorbidities mainly diabetes mellitus. BP was controlled in 37% of patients. Treatment was intensified for 23% patients with uncontrolled BP. In multivariable (logistic regression) analysis, determinants positively associated with controlled BP were treatment at general hospitals (OR 1.89, 95% CI 1.26 to 2.83) compared with specialised hospitals and longer treatment duration (OR 1.04, 95% CI 1.01 to 1.06). Negatively associated determinants were previously uncontrolled BP (OR 0.30, 95% CI 0.21 to 0.43), treatment regimens with diuretics (OR 0.68, 95% CI 0.50 to 0.94) and age (OR 0.99, 95% CI 0.98 to 1.00). The only significant-positive-determinant for treatment intensification was duration of therapy (OR 1.05, 95% CI 1.02 to 1.09)., Conclusions: The level of controlled BP and treatment intensification practice in this study was low. The findings suggest the need for in-depth understanding and interventions of the identified determinants such as uncontrolled BP on consecutive visits, older age and type of hospital., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Several methods have been developed to conduct and support medication reviews in older persons with multimorbidity. Assessing the patient's priorities for achieving specific health outcomes can guide the medication review process. Little is known about the impact of conducting such assessments., Aim: This pilot study aimed to determine proposed and observed medication changes when using an outcome prioritisation tool (OPT) during a medication review in general practice., Design and Setting: Participants were older patients with multimorbidity (aged ≥69 years) with polypharmacy (five or more chronic medications) from the practices of 14 GPs., Method: Patients were asked to prioritise four universal health outcomes - remaining alive, maintaining independence, reducing pain, and reducing other symptoms - using an OPT. GPs used this prioritisation to review the medication and to propose and discuss medication changes with the patient. The outcomes included the proposed medication change as documented by the GP, and the observed medication change in the electronic health record at follow-up. Descriptive analyses were conducted to determine medication changes according to the prioritised health outcomes., Results: A total of 59 patients using 486 medications prioritised the four health outcomes. GPs proposed 34 changes of medication, mainly stopping, for 20 patients. At follow-up, 14 medication changes were observed for 10 patients. The stopping of medication (mostly preventive) was particularly observed in patients who prioritised 'reducing other symptoms' as most important., Conclusion: Using an OPT leads mainly to the stopping of medication. Medication changes appeared to be easiest for patients who prioritised 'reducing other symptoms' as most important., (© British Journal of General Practice 2017.)

Objectives: To explore an outcome prioritization tool (OPT) in eliciting individuals' preferred health outcomes (remaining alive, maintaining independence, reducing pain, reducing other symptoms) in the context of medication review in family practice., Design: Cross-sectional pilot study with mixed-methods design., Setting: Family practice., Participants: Multimorbid individuals (N = 60; aged ≥69) with polypharmacy (≥5 chronic medications) derived from the practice lists of a purposive sample of 13 family physicians (FPs)., Measurements: Participants were asked to prioritize each health outcome according the trade-off principle, and FPs used this prioritization for medication review. The acceptability and practicality were measured using a questionnaire for FPs and participants and semistructured interviews with FPs., Results: Ninety-two percent of participants found the OPT understandable, and 55% could easily prioritize between health outcomes. Working with the OPT (mean duration 31 minutes) was a new approach for FPs, but they became more adept at using it. For FPs, the OPT provides better understanding of their patients. Participants and FPs thought that there should be a specific reason to discuss preferences, such as (expected) decline in health status., Conclusion: The OPT appears to be promising in eliciting patient preferences but is not suitable for routine medication review at present. Further optimization before actual use is needed (e.g., knowledge in which clinical situations the OPT is useful). More information is needed on how individuals and their families perceive the tool., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Aim: Details of data quality and how quality issues were solved have not been reported in published comparative effectiveness studies using electronic health record data., Methods: We developed a conceptual framework of data quality assessment and preprocessing and apply it to a study comparing angiotensin-converting enzyme inhibitors with angiotensin receptor blockerss on renal function decline in diabetes patients., Results: The framework establishes a line of thought to identify and act on data issues. The core concept is to evaluate whether data are fit-for-use for research tasks. Possible quality problems are listed through specific signal detections, and verified whether they are true problems. Optimal solutions are selected for the identified problems., Conclusion: This framework can be used in observational studies to improve validity of results.

Aim: To compare effectiveness of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) for protecting Type 2 diabetes mellitus (DM2) patients from renal function decline in a real-world setting., Methods: Retrospective cohort study of new ACEi/ARB users in 2007-2012 in an unselected primary care DM2 population. Outcome is decline in renal function stage (combining estimated glomerular filtration rate and albuminuria). Patients were matched on a propensity score. Extended Cox models with time-varying covariates were used to estimate hazard ratios of outcome., Results: The time to renal function decline for ARB users was slightly, but not significantly longer than for ACEi users (hazard ratio: 0.80; 95% CI: 0.58-1.10; p = 0.166)., Conclusion: This study did not show significant differences between the classes in preventing renal function decline in DM2 patients in primary care.

Objectives: To assess whether patients' willingness to add a blood pressure-lowering drug and the importance they attach to specific treatment characteristics differ among age groups in patients with type 2 diabetes., Materials and Methods: Patients being prescribed at least an oral glucose-lowering and a blood pressure-lowering drug completed a questionnaire including a discrete choice experiment. This experiment contained choice sets with hypothetical blood pressure-lowering drugs and a no additional drug alternative, which differed in their characteristics (i.e. effects and intake moments). Differences in willingness to add a drug were compared between patients <75 years (non-aged) and ≥75 years (aged) using Pearson χ²-tests. Multinomial logit models were used to assess and compare the importance attached to the characteristics., Results: Of the 161 patients who completed the questionnaire, 151 (72%) could be included in the analyses (mean age 68 years; 42% female). Aged patients were less willing to add a drug than non-aged patients (67% versus 84% respectively; P = 0.017). In both age groups, the effect on blood pressure was most important for choosing a drug, followed by the risk of adverse drug events and the risk of death. The effect on limitations due to stroke was only significant in the non-aged group. The effect on blood pressure was slightly more important in the non-aged than the aged group (P = 0.043)., Conclusions: Aged patients appear less willing to add a preventive drug than non-aged patients. The importance attached to various treatment characteristics does not seem to differ much among age groups.

Background: Evidence from developed countries showed that medication errors are common and harmful. Little is known about medication errors in resource-restricted settings, including Vietnam., Objectives: To determine the prevalence and potential clinical outcome of medication preparation and administration errors, and to identify factors associated with errors., Methods: This was a prospective study conducted on six wards in two urban public hospitals in Vietnam. Data of preparation and administration errors of oral and intravenous medications was collected by direct observation, 12 hours per day on 7 consecutive days, on each ward. Multivariable logistic regression was applied to identify factors contributing to errors., Results: In total, 2060 out of 5271 doses had at least one error. The error rate was 39.1% (95% confidence interval 37.8%- 40.4%). Experts judged potential clinical outcomes as minor, moderate, and severe in 72 (1.4%), 1806 (34.2%) and 182 (3.5%) doses. Factors associated with errors were drug characteristics (administration route, complexity of preparation, drug class; all p values < 0.001), and administration time (drug round, p = 0.023; day of the week, p = 0.024). Several interactions between these factors were also significant. Nurse experience was not significant. Higher error rates were observed for intravenous medications involving complex preparation procedures and for anti-infective drugs. Slightly lower medication error rates were observed during afternoon rounds compared to other rounds., Conclusions: Potentially clinically relevant errors occurred in more than a third of all medications in this large study conducted in a resource-restricted setting. Educational interventions, focusing on intravenous medications with complex preparation procedure, particularly antibiotics, are likely to improve patient safety.

Objective: Identifying key features in individual case safety reports (ICSR) of suspected adverse drug reactions (ADRs) with cardiometabolic drugs from sub-Saharan Africa (SSA) compared with reports from the rest of the world (RoW)., Methods: Reports on suspected ADRs of cardiometabolic drugs (ATC: A10[antidiabetic], B01[antithrombotics] and C[cardiovascular]) were extracted from WHO Global database, VigiBase(®) (1992-2013). We used vigiPoint, a logarithmic odds ratios (log2 OR)-based method to study disproportional reporting between SSA and RoW. Case-defining features were considered relevant if the lower limit of the 99% CI > 0.5., Results: In SSA, 3773 (9%) of reported ADRs were for cardiometabolic drugs, in RoW for 18%. Of these, 79% originated from South Africa and 81% were received after 2007. Most reports were for drugs acting on the renin-angiotensin system (36% SSA & 14% RoW). Compared with RoW, reports were more often sent for patients 18-44 years old (log2 OR 0.95 [99 CI 0.80; 1.09]) or with non-fatal outcome (log2 OR 1.16 [99 CI 1.10; 1.22]). Eight ADRs (cough, angioedema, lip swelling, face oedema, swollen tongue, throat irritation, drug ineffective and blood glucose abnormal) and seven drugs (enalapril, rosuvastatin, perindopril, vildagliptin, insulin glulisine, nifedipine and insulin lispro) were disproportionally more reported in SSA than in the RoW., Conclusions: 'In recent years, the number of adverse drug reactions (ADRs) reported in Sub-Saharan Africa (SSA) has sharply increased. The data showed the well-known population-based differential ADR profile of ACE inhibitors in the SSA population.', (© 2015 John Wiley & Sons Ltd.)

Aims: To compare the values regulators attach to different drug effects of oral antidiabetic drugs with those of doctors and patients., Methods: We administered a 'discrete choice' survey to regulators, doctors and patients with type 2 diabetes in The Netherlands. Eighteen choice sets comparing two hypothetical oral antidiabetic drugs were constructed with varying drug effects on glycated haemoglobin, cardiovascular risk, bodyweight, duration of gastrointestinal complaints, frequency of hypoglycaemia and risk of bladder cancer. Responders were asked each time which drug they preferred., Results: Fifty-two regulators, 175 doctors and 226 patients returned the survey. Multinomial conditional logit analyses showed that cardiovascular risk reduction was valued by regulators positively (odds ratio 1.98, 95% confidence interval 1.11-3.53), whereas drug choices were negatively affected by persistent gastrointestinal problems (odds ratio 0.24, 95% confidence interval 0.14-0.41) and cardiovascular risk increase (odds ratio 0.49, 95% confidence interval 0.27-0.87). Doctors and patients valued these effects in a similar manner to regulators. The values that doctors attached to large changes in glycated haemoglobin and that both doctors and patients attached to hypoglycaemia and weight gain also reached statistical significance. No group's drug choice was affected by a small absolute change in risk of bladder cancer when presented in the context of other drug effects. When comparing the groups, the value attached by regulators to less frequent hypoglycaemic episodes was significantly smaller than by patients (P = 0.044)., Conclusions: Regulators may value major benefits and risks of drugs for an individual diabetes patient mostly in the same way as doctors and patients, but differences may exist regarding the value of minor or short-term drug effects., (© 2014 The British Pharmacological Society.)

Purpose: To assess the validity of a patient-reported adverse drug events (ADEs) questionnaire with a 3-month or 4-week recall period., Methods: Patients receiving at least one oral glucose-lowering drug were asked to report potential ADEs they experienced related to any drug in a daily diary for a 3-month period. Thereafter, they completed the ADE questionnaire with either a 3-month or 4-week recall period. The validity was assessed by comparing ADEs reported in each version with those reported in the diary at class level and at specific ADE level. At class level, a comparison was made using (1) primary system organ classes (SOCs) of the medical dictionary for regulatory activities and (2) other related SOCs. Sensitivity and positive predictive value (PPV) were calculated., Results: Each version of the questionnaire was completed by 39 patients. In the 3-month group, 21 patients reported 70 ADEs in the diary. In the 4-week group, six patients reported seven ADEs in the last 4 weeks of the diary. Sensitivity to assess ADEs at primary SOC was low for both recall groups (33 %). PPV was 51 and 10 % for, respectively, the 3-month and 4-week group. Taking other related SOCs into account slightly increased the sensitivity for the 3-month group (38%). Sensitivity of reporting the same ADE was 41 and 43 % for, respectively, the 3-month and 4-week group., Conclusions: Regardless of the recall period and level of comparison, the validity for assessing ADEs was low with the patient-reported ADE questionnaire. Further refinement is needed to improve the validity.

Background: Direct patient-reported information about adverse drug events (ADEs) is important since it adds to healthcare professional-reported information about the safety of drugs. Previously, we developed an instrument to assess patient-reported ADEs in research settings. The aim of this study is to assess the construct and concurrent validity of the questionnaire., Methods: Patients on at least an oral glucose-lowering drug completed the ADE questionnaire, the World Health Organization Quality of Life-BREF, and the Treatment Satisfaction Questionnaire for Medication (TSQM). The ADE questionnaire assesses ADEs for any drug that the patient uses. Construct validity was assessed by testing whether patients reporting an ADE had a lower general quality of life and physical health than those not reporting an ADE, using Mann-Whitney U-tests and t-tests (significance level <0.05). For concurrent validity, we tested whether ADEs that patients associate with particular drugs in the ADE questionnaire are documented in the Summary of Product Characteristics (SPC) of those drugs, and whether patients who report an ADE with the use of metformin on the TSQM, mention metformin as a drug associated with an ADE on the ADE questionnaire. Agreement of 70% with the SPC was considered satisfactory. Sensitivity and positive predictive value (PPV) were calculated for the comparison with the TSQM, where 70% was used as the cut-off level for sufficient concurrent validity., Results: We included 135 patients (mean age 64 years, 35% women). Patients who reported an ADE (N = 37) had a lower general quality of life and physical health than those not reporting an ADE (P < 0.05). For 78 of the 146 reported ADEs (53%), patients mentioned at least 1 particular drug associated with the ADE. After clustering related ADEs, this resulted in 56 patient-reported ADE-drug associations. Of these, 41 (73%) were in agreement with information in the SPC. Finally, the questionnaire had a sensitivity of 38% and PPV of 79% for assessing ADEs associated with metformin., Conclusions: The construct validity of the patient-reported ADE questionnaire was sufficient for reporting any versus no ADE, but the concurrent validity was only partly demonstrated. Therefore, the questionnaire needs to be adapted before it can be used.

Introduction: Prescribing medication is an important aspect of almost all in-hospital treatment regimes. Besides their obviously beneficial effects, medicines can also cause adverse drug events (ADE), which increase morbidity, mortality and health care costs. Partially, these ADEs arise from medication errors, e.g. at the prescribing stage. ADEs caused by medication errors are preventable ADEs. Until now, medication ordering was primarily a paper-based process and consequently, it was error prone. Computerized Physician Order Entry, combined with basic Clinical Decision Support System (CPOE/CDSS) is considered to enhance patient safety. Limited information is available on the balance between the health gains and the costs that need to be invested in order to achieve these positive effects. Aim of this study was to study the balance between the effects and costs of CPOE/CDSS compared to the traditional paper-based medication ordering., Methods: The economic evaluation was performed alongside a clinical study (interrupted time series design) on the effectiveness of CPOE/CDSS, including a cost minimization and a cost-effectiveness analysis. Data collection took place between 2005 and 2008. Analyses were performed from a hospital perspective. The study was performed in a general teaching hospital and a University Medical Centre on general internal medicine, gastroenterology and geriatric wards. Computerized Physician Order Entry, combined with basic Clinical Decision Support System (CPOE/CDSS) was compared to a traditional paper based system. All costs of both medication ordering systems are based on resources used and time invested. Prices were expressed in Euros (price level 2009). Effectiveness outcomes were medication errors and preventable adverse drug events., Results: During the paper-based prescribing period 592 patients were included, and during the CPOE/CDSS period 603. Total costs of the paper-based system and CPOE/CDSS amounted to €12.37 and €14.91 per patient/day respectively. The Incremental Cost-Effectiveness Ratio (ICER) for medication errors was 3.54 and for preventable adverse drug events 322.70, indicating the extra amount (€) that has to be invested in order to prevent one medication error or one pADE., Conclusions: CPOE with basic CDSS contributes to a decreased risk of preventable harm. Overall, the extra costs of CPOE/CDSS needed to prevent one ME or one pADE seem to be acceptable., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Little is known about interventions to reduce intravenous medication administration errors in hospitals, especially in low- and middle-income countries., Objective: To assess the effect of a clinical pharmacist-led training programme on clinically relevant errors during intravenous medication preparation and administration in a Vietnamese hospital., Methods: A controlled before and after study with baseline and follow-up measurements was conducted in an intensive care unit (ICU) and a post-surgical unit (PSU). The intervention comprised lectures, practical ward-based teaching sessions and protocols/guidelines, and was conducted by a clinical pharmacist and a nurse. Data on intravenous medication preparation and administration errors were collected by direct observation 12 h/day for seven consecutive days. Generalised estimating equations (GEE) were used to assess the effect of the intervention on the prevalence of clinically relevant erroneous doses, corrected for confounding factors., Results: 1204 intravenous doses were included, 516 during the baseline period (236 on ICU and 280 on PSU) and 688 during the follow-up period (407 on ICU and 281 on PSU). The prevalence of clinically relevant erroneous doses decreased significantly on the intervention ward (ICU) from 64.0% to 48.9% (p<0.001) but was unchanged on the control ward (PSU) (57.9% vs 64.1%; p=0.132). GEE analysis showed that doses on the intervention ward were 2.60 (1.27-5.31) times less likely to have clinically relevant errors (p=0.013)., Conclusions: The pharmacist-led training programme was effective, but the error rate remained relatively high. Further quality improvement strategies are needed, including changes to the working environment and promotion of a safety culture.